Obesity and the constellation of associated metabolic risk factors (atherogenic dyslipidemia, hyperglycemia, hypertension, hepatic steatosis, prothrombotic and proinflammatory states) contribute importantly to death and disability in the United States. The mechanisms responsible for obesity and the metabolic syndrome have resisted elucidation through conventional approaches. Experts in the field have proposed that progress towards understanding the gene/environment interactions causing obesity will require the implementation of a broad-based clinical and basic research program. To develop such a program, we have assembled a highly interactive and collaborative interdisciplinary team of experts at UT Southwestern called the Taskforce for Obesity Researchat Southwestern (TORS). TORS harnesses expertise from highly diverse disciplines, with a goal of defining the behavioral, metabolic, genetic and molecular mechanisms contributing to obesity and the metabolic syndrome. Our accomplishments during the past 2 years of P20 funding demonstrate that we have successfully integrated traditionally disparate disciplines of anatomy, biochemistry, chemistry, genetics, lipid metabolism, molecular biology, intermediary metabolism, neuroendocrinology, nutrition, pharmacology, physiology, and clinical epidemiology into a cohesive Interdisciplinary Research Consortium to study obesity and the metabolic syndrome. The strength of our faculty and the support of our administration provide TORS with the expertise, infrastructure, and ability to develop new approaches to the elucidation and prevention of obesity-associated diseases. Successful completion of the studies described in this grant will provide much needed insights into the key molecules and pathways that govern whole-body energy metabolism, which will be translated into the development of new approaches to prevent obesity and to treat the metabolic complications of this disorder.